1. Field of the Invention
This invention relates to the production and recovery of alkaloid compounds by cell culture of the tissues of the conifer, Taxus brevifolia and other species of Taxus.
2. Description of Prior Art
Among the alkaloids which have been isolated from T. brevifolia plant material are taxol and a number of its derivatives [Horwitz et al., Ann. New York Acad. Sci. 466: 733-745 (1986); Suffness et al., In "The Alkaloids," Brossi, A. (ed.), Chemistry and Pharmacology 25: 6-18, 280-288 (1985)]. Taxol has been found to exhibit significant antitumor activity in a variety of cell lines, including B16 melanoma and Mx-1 mammary xenograft. Taxol completed Phase I clinical trials and in 1985 was approved for broader efficacy studies in Phase II trails. Phase II studies in ovarian cancer have shown taxol to be effective, with a response rate of 30% [Rowinsky et al., Proc. Am. Soc. Clin. Oncologists 7: 136, Abstr. 523 (1988)]. Some results were seen in patients with melanoma as well [Einsig et al., Proc. Am. Soc. Clin. Oncologists 7: 249, Abstr. 963 (1988)]. The mode of action of taxol is thought to be novel.
Continued testing of the drug and subsequent commercial applications of chemotherapy require quantities which cannot be obtained from the scarce natural source. Taxol is a complex compound, and attempts at chemical synthesis to date have been unsuccessful. Preparation of derivatives will depend on a supply of the parent compound from natural sources. The T. brevifolia tree is rare, has slow growth, and is not cultivated. Ten thousand pounds of bark are required to produce one pound of taxol. The extraction of the bark is complicated, and product variability occurs.